Prolactin is a polypeptide hormone with over 300 separate biological activities and its serum level is increased during pregnancy and lactation. It has been described that pregnancy and lactation affect drug and steroid metabolism in mice and humans. Several studies reported that pregnancy or lactation influences liver cytochrome P450 (Cyp) expression and its activity, affecting the biosynthesis of steroids and xenobiotics through growth hormone or sex hormones; however, the role of prolactin as the regulator of liver Cyp expression has not been elucidated so far. In the present study, we focused on prolactin as the regulator of liver sex-predominant gene expressions including Cyps. To investigate the role of prolactin in the hepatic gene expressions, pCAGGS expression vector containing mouse prolactin cDNA was transfected by hydrodynamic injection in both male and female mice. Hyperprolactinemia phosphorylated signal transducer and activator of transcription 5 in the liver and augmented female mice liver mRNA expressions of Cyp3a16, Cyp3a41, Cyp3a44, Cyp2b9 and prolactin receptor genes, whose expressions were female-predominant in hepatocytes. Moreover, liver expressions of male-predominant genes such as Cyp2d9, Cyp7b1, Mup1 and Alas2 were reduced in male mice with hyperprolactinemia. The serum levels of conventional regulators in hepatic gene expressions, growth hormone and testosterone, were not affected by hyperprolactinemia. We demonstrated that prolactin up-regulated female-predominant genes in female mice and down-regulated male-predominant genes in male mice. We conjecture that higher concentration of prolactin would alter the steroids and xenobiotic metabolisms by modulating hepatic Cyp gene expressions during pregnancy and lactation.
- The American Society for Pharmacology and Experimental Therapeutics